PB2217: REAL-WORLD RESEARCH OF CLINICAL AND HEMATOLOGIC NEOPLASMS RELATED GENETIC MUTATIONS IN 275 POLYCYTHEMIA VERA PATIENTS
Authors: Lan Zhang, Shenjie Wang, Keyi Jin, Jie Jin, Jian Huang
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Polycythemia vera (PV) is one of the myeloproliferative neoplasms (MPNs) characterized by the overproduction of morphologically and functionally normal blood cells. Whereas, the relationship between hematologic neoplasms related genetic mutations and clinical characteristics is still under investigation. Aims: This study aimed to explore the impact of JAK2 gene mutational status and allele burden, WT1 gene expression level and hematologic neoplasms related genetic mutations on clinical characteristics and prognosis of polycythemia vera (PV). Methods: We retrospectively reviewed the clinical parameters and hematologic information of 275 patients in China from January 2015 to August 2022 (ChiCTR2200061208), and analyzed the relationship between JAK2 gene mutation, WT1 gene expression level, hematologic neoplasms related genetic mutations and clinical characteristics of polycythemia vera. Results: Patients with JAK2V617F mutation (A) had the oldest onset age(vs B, P=0.036; vs C, P<0.001), patients with JAK2 exon12 mutation (B) had the highest hemoglobin values(vs A, P=0.031; vs C, P=0.010), and JAK2 unmutated patients (C) had the lowest leukocyte counts(vs A, P<0.001; vs B, P=0.024) and lactate dehydrogenase level(vs A, P<0.001; vs B, P<0.001) (FigureA). JAK2 V617F allele burden was positively correlated with the age of onset(P=0.001, r=0.251), leukocyte counts(P<0.001, r=0.466) and lactate dehydrogenase values(P<0.001, r=0.320) (FigureB). Patients with PV had higher expression level of WT1 than patients with non-hematologic malignancies(P<0.001) (FigureC), and the expression level of WT1 was positively correlated with lactate dehydrogenase value(P=0.011, r=0.460), JAK2V617F allele burden(P=0.004, r=0.528) and fibrosis grade of bone marrow(P=0.044, r=0.390)(FigureD). JAK2 mutated PV patients was more likely to have genetic mutations than JAK2 unmutated patients(P=0.002)(FigureE, F, G). Patients with no less than 3 genetic mutations(P=0.028) and patients with TET2 gene mutation(P=0.001) had higher frequency of splenomegaly (FigureH). Summary/Conclusion: PV patients with different JAK2 gene mutational status had various clinical characteristics. JAK2 V617F allele burden was positively correlated with the age of onset, leukocyte counts and lactate dehydrogenase values. WT1 gene is overexpressed in PV, and the expression level of WT1 was positively correlated with JAK2V617F allele burden. JAK2 mutated PV patients was more likely to have genetic mutations than JAK2 unmutated patients. Patients with no less than 3 genetic mutations and patients with TET2 gene mutation had higher frequency of splenomegaly. This research was funded by Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09; Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011. *Correspondence to: Prof Jian Huang; Prof Jie JinKeywords: Mutation, WT1, Polycythemia vera, Clinical data